Genotype 1a NS5A RAS | SHARED - A Hepatitis C Resource

	Daclastasvir in GT1a		Ledipasvir in GT1a		Velpatasvir in GT1a		Ombitasvir in GT1a		Pibrentasvir in GT1a		Elbasvir in GT1a
Mutation	EC50 FC-/Clinical RAS	Phenotype	EC50 FC-/Clinical RAS	Phenotype	EC50 FC-/Clinical RAS	Phenotype	EC50 FC-/Clinical RAS	Phenotype	EC50 FC-/Clinical RAS	Phenotype	EC50 FC-/Clinical RAS	Phenotype
WT (1a_H77)	1x[1, 2]	likely susceptible	1x[1, 3]	likely susceptible	1x	likely susceptible	1x	likely susceptible	1x	likely susceptible	1x	likely susceptible
T21I	1x[4]	likely susceptible
K24A	<2.5x[5]	likely susceptible			<2.5x	likely susceptible
K24E	<2.5x[5]	likely susceptible			<2.5x	likely susceptible			cRAS	resistance possible
K24G			10- 50x[3, 6-9]	likely susceptible	<2.5x	likely susceptible
K24M					cRAS	resistance possible
K24N	<2.5x[5, 9]	likely susceptible	10- 50x[6, 8, 9]	likely susceptible	<2.5x	likely susceptible					0.4x	likely susceptible
K24Q	<2.5x[5]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible			cRAS	resistance possible
K24R	2x[3, 5, 9, 10]/cRAS[10]	resistance possible	4x[3, 6, 8, 9, 11, 12]/cRAS[7, 11-13]	resistance possible	1.1x	likely susceptible	1x/cRAS	resistance possible	0.3x/cRAS	resistance possible	1x/cRAS	resistance possible
K24S	<2.5x[5]	likely susceptible	<2.5x	likely susceptible	<2.5x	likely susceptible
K24T	205x[3, 5]	resistance likely	<2.5x	likely susceptible	<2.5x/cRAS	resistance possible					0.4x	likely susceptible
A25T	<2.5x	likely susceptible	<2.5x	likely susceptible	<2.5x	likely susceptible
K26E	<2.5x[5]	likely susceptible			<2.5x	likely susceptible
M28A	4591x[5, 9, 14-16]/cRAS[4, 17]	resistance likely	>1000x[5, 6, 9, 12]/cRAS[12, 13]	resistance likely	2.5 - 100x	resistance possible	cRAS	resistance possible	2x/cRAS	resistance possible	61x/cRAS	resistance likely
M28I	1x[5, 16]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
M28G	>100x[5, 9, 18]/cRAS[18]	resistance likely	>1000x[5-9]	resistance likely	>100x	resistance likely			244x/cRAS	resistance likely	71429x/cRAS	resistance likely
M28S									cRAS	resistance possible
M28T	205x[2, 5, 9, 16, 17]/cRAS[16, 17]	resistance likely	61x[1, 3, 6, 8, 9, 11, 12]/cRAS[7, 11-13]	resistance likely	8x/cRAS	resistance likely	8965x/cRAS	resistance likely	2.1x/cRAS	resistance possible	15x/cRAS	resistance likely
M28L	<2.5x[5]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
M28V	1x[3, 5, 9, 14, 16]/cRAS[16, 17]	resistance possible	0.6x[3, 8, 9, 12, 15]/cRAS[7, 12]	resistance possible	1.3x/cRAS	resistance possible	58x/cRAS	resistance likely	1.8x/cRAS	resistance possible	1x/cRAS	resistance possible
P29Q									cRAS	resistance possible
P29R									cRAS	resistance possible
Q30C	<2.5x[5]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
Q30D	90000-333000x[9, 16, 17]/cRAS	resistance likely							94x	resistance likely	925x	resistance likely
Q30del									3549x	resistance likely
Q30E	7500x[2, 5, 9, 15, 17, 18]/cRAS[4, 17]	resistance likely	5458x[1, 3, 5, 6, 9, 15]/cRAS[13]	resistance likely	37x/cRAS	resistance likely	1340x/cRAS	resistance likely	2.4x/cRAS	resistance possible	56x	resistance likely
Q30G	2055-8500x[5, 9, 16, 17]/cRAS[4, 17]	resistance likely	100-1000x[5, 6, 8, 9]	resistance likely	2.5 - 100x	resistance possible			1.3x/cRAS	resistance possible	84x	resistance likely
Q30H	435x[2, 3, 5, 9, 15-17]/cRAS[2, 4, 16, 17]	resistance likely	183x[1, 3, 5, 6, 8, 9, 11, 12]/cRAS[7, 11-13]	resistance likely	2x/cRAS	resistance possible	3x	likely susceptible	1x/cRAS	resistance possible	8x/cRAS	resistance likely
Q30I	<2.5x[5]	likely susceptible	2.5-10x[12]	likely susceptible	<2.5x	likely susceptible
Q30K	24545x[5, 9, 14, 16, 17]/cRAS[2, 16, 17]	resistance likely	>1000x[3, 5-7, 9, 11, 12]/cRAS[7, 11-13]	resistance likely	10x/cRAS	resistance likely	183x/cRAS	resistance likely	1x/cRAS	resistance possible	62x/cRAS	resistance likely
Q30L	4x[5, 9, 19]	likely susceptible	2.5 - 10x[3, 6-9, 11, 12, 19]/cRAS[7, 11-13]	resistance possible	0.5x/cRAS	resistance possible	<1x	likely susceptible	0.3x/cRAS	resistance possible	1x/cRAS	resistance possible
Q30N	1100x[9, 16, 19]/cRAS[4]	resistance likely	>100x[19]	resistance likely			<5x	likely susceptible	cRAS	resistance possible	cRAS
Q30P	1x[4]	likely susceptible
Q30R	365x[2, 3, 5, 9, 15-17]/cRAS[2, 4, 17]	resistance likely	632x[1, 3, 5, 6, 8, 11, 12, 15]/cRAS[11-13]	resistance likely	2x/cRAS	resistance possible	800x/cRAS	resistance likely	1.7x/cRAS	resistance possible	125x/cRAS	resistance likely
Q30S					<2.5x	likely susceptible
Q30T	15x[9, 16, 17, 19]/cRAS[17]	resistance possible	2.5-10x[6, 8, 11]/cRAS[11]	resistance possible	1x/cRAS	resistance possible	0.4x	likely susceptible
Q30V	<2.5x[5]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
Q30Y	>1000x[5, 19]	resistance likely	>1000x[5, 12, 19]/cRAS[12, 13]	resistance likely	<2.5x	likely susceptible	172x	resistance likely	0.8x	likely susceptible	cRAS	resistance possible
L31F					2.5 - 100x	resistance possible					96x/cRAS	resistance likely
L31I	166x[9, 16, 17, 19]/cRAS[17]	resistance likely	200x[5, 11, 12, 19]/cRAS[11, 12]	resistance likely	4x/cRAS	resistance likely	6x	likely susceptible			134x/cRAS	resistance likely
L31M	250x[3, 5, 9, 16-18]/cRAS[4, 16, 17]	resistance likely	554x[1, 3, 5, 8, 9, 11, 12, 15, 18]/cRAS[7, 11-13]	resistance likely	16x/cRAS	resistance likely	2x	likely susceptible	1.1x-1.3x/cRAS	resistance possible	10x/cRAS	resistance likely
L31P			cRAS[12, 13]	resistance possible
L31V	1000x[2, 5, 9, 16, 17]/cRAS[2, 17]	resistance likely	133x[5, 8, 9, 11, 12]/cRAS[11, 20]	resistance likely	129x/cRAS	resistance likely	155x	resistance likely	1.3x	resistance possible	61x/cRAS	resistance likely
P32L	233x[5, 9]	resistance likely	>100x[5, 6, 8, 9, 11]	resistance likely	28x/cRAS	resistance likely	44x	resistance possible	1.7x	likely susceptible
P32S
P32del										resistance possible
F36L									0.9x	likely susceptible
V37A	1x[4]	likely susceptible
V37M	1x[4]	likely susceptible
S38F			50 - 100x[6, 11, 12]/cRAS[12, 13]	resistance likely	<2.5x	likely susceptible
S38T	<2.5x[5]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
S38Y					cRAS	resistance possible
H54C	0.5x[16]	likely susceptible
H54N	0.1x[9, 16, 19]	likely susceptible
H54R	cRAS[2, 16]	resistance possible
H54Y	1.2x[4]/cRAS[4]	resistance possible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible	cRAS	resistance possible
H58C	0.5x[5, 16]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible			0.9x/cRAS	resistance possible
H58D	500x[3, 5, 9, 14, 16, 18]/cRAS[4, 16, 17]	resistance likely	1127x[1, 3, 5, 6, 8, 9, 15, 18]/cRAS[21]	resistance likely	7x/cRAS	resistance likely	243x/cRAS	resistance likely	1.1x/cRAS	resistance possible	6x/cRAS	resistance likely
H58L	<2.5x[5]	likely susceptible			<2.5x	likely susceptible
H58N	1.3x[5, 16]	likely susceptible			<2.5x/cRAS	resistance possible			cRAS
H58P	1.2x[3, 5, 9, 14, 16]/cRAS[16]	resistance possible	1x[3, 5, 12]/cRAS[12]	resistance possible	<1x/cRAS[22]	resistance possible	0.5x/cRAS	resistance possible	0.6x	likely susceptible
H58Q	0.5x[5, 16]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
H58R	0.3x[5]	likely susceptible	<2.5x[5, 12]/cRAS[12]	resistance possible	<2.5x/cRAS	resistance possible	cRAS	resistance possible	0.7x	likely susceptible
H58S	0.7x[16]	likely susceptible
H58V	cRAS[4]	resistance possible
H58Y	0.5x[5, 16]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible			cRAS	resistance possible
A61S
A61V
E62A									5x/cRAS	resistance likely
E62D	4x[5, 16]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible	cRAS	resistance possible	0.6x	likely susceptible	cRAS	resistance possible
E62G	0.7x[5, 16]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
E62Q	0.8x[16]	likely susceptible
E62R	<2.5x[5]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
E62V	1.7x[16]	likely susceptible
R81K	<2.5x[5]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
R81M											1x	likely susceptible
R81S											1x	likely susceptible
R81W	<2.5x[5]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible					1x	likely susceptible
S85N					cRAS	resistance possible
I90V	<2.5x[5]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
A92K	>100x[5, 9]	resistance likely	>100x[5]	resistance likely	>100x	resistance likely
A92P	cRAS[4, 9]	resistance possible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible					1x	likely susceptible
A92V	<2.5x[5]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
A92T	<2.5x[5]	likely susceptible	10- 50x[6, 8, 9]	likely susceptible	<2.5x	likely susceptible			0.4x	likely susceptible
Y93C	555x[2, 5, 9, 14-17]/cRAS[2, 4, 17]	resistance likely	1602x[1, 5, 6, 8, 9, 11, 12, 15]/cRAS[11-13, 21]	resistance likely	11x/cRAS	resistance likely	1675x/cRAS	resistance likely	1.7x	likely susceptible	50x/cRAS	resistance likely
Y93D									unfit
Y93F	66.7x[9, 16, 19]	resistance possible	10- 50x[6, 8, 9, 12]/cRAS[12]	resistance possible	<2.5x	likely susceptible	27x/cRAS	resistance likely	0.9x	likely susceptible	2x	likely susceptible
Y93H	1600x[2, 3, 5, 9, 15-18]/cRAS[17]	resistance likely	1677x[1, 3, 5, 6, 8, 9, 11, 12, 15, 18]/cRAS[7, 11-13]	resistance likely	609x/cRAS	resistance likely	41383x/cRAS	resistance likely	7x/cRAS	resistance likely	220x/cRAS	resistance likely
Y93L			>100x[5]	resistance likely	2.5 -100x	resistance possible	3006x/cRAS	resistance likely	1.2x	likely susceptible
Y93N	14100x[2, 5, 9, 15-18]/cRAS[2, 17]	resistance likely	>14706x[3, 5, 6, 8, 11, 12, 15]/cRAS[7, 11-13]	resistance likely	2758x/cRAS	resistance likely	66740x/cRAS	resistance likely	7x/cRAS	resistance likely	929x/cRAS	resistance likely
Y93R	cRAS[4, 9]	resistance possible	>100x[5]	resistance likely	497x/cRAS	resistance likely
Y93S	7,000x[5, 9, 16, 19]/cRAS[4]	resistance likely	>1000x[5, 6, 8, 9]	resistance likely	64x/cRAS	resistance likely	1013x/cRAS	resistance likely	1.6x	likely susceptible	cRAS	resistance possible
Y93T	>100x[5, 9]	resistance likely	100-1000x[5, 12]	resistance likely	2.5 - 100x	resistance possible
Y93W			>100x[5]	resistance likely	999x/cRAS	resistance likely
P97S	<2.5x[5]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
I121V
L138I	<2.5x[5]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
L153V					cRAS	resistance possible
F161Y
E171D						resistance possible
T213A [Conflicting WT]					cRAS	resistance possible
L255I				resistance possible
I269V							1x	likely susceptible
H340Y	<2.5x[5]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
S366L	<2.5x[5]	likely susceptible	<2.5x[5]	likely susceptible	<2.5x	likely susceptible
V371I/M
A377T [Conflicting WT]						resistance possible
D392N
D427N											cRAS	resistance possible
V442T						resistance possible
T21I+L31M	538x[4]	resistance likely
K24Q+H58D			>100x[5]	resistance likely	<2.5x	likely susceptible
K24Q+Q30R			>100x[5]	resistance likely	<2.5x	likely susceptible
K24R+L31M			>100x[5]	resistance likely
K24R+Q30H			>100x[5]	resistance likely
K24R+H58D			>100x[5]	resistance likely
K24R+H58P					<2.5x	likely susceptible
K24R+M28T							3216x	resistance likely	0.6x	likely susceptible
K24R+M28V					<2.5x	likely susceptible	44x	resistance likely	0.6x	likely susceptible
K24R+Q30R			>100x[5]	resistance likely			950x	resistance likely	0.4x	likely susceptible
K24R+Y93C			>100x[5]	resistance likely
K24R+Y93F			>100x[5]	resistance likely
A25T+Q30R					<2.5x	likely susceptible
A25T+H58P			<2.5x[5]	likely susceptible	<2.5x	likely susceptible
M28A+H58R					<2.5x	likely susceptible
M28A+M28T					25x	resistance likely
M28A+Q30H											1429x	resistance likely
M28A+Q30K	348,333x[16]	resistance likely
M28A+Q30L			>100x[5]	resistance likely	>100x	resistance likely
M28A+Q30R	284000x[16]	resistance likely	>100x[5]	resistance likely	>100x	resistance likely
M28G+H58R			>100x[5]	resistance likely	>100x	resistance likely
M28G+Q30R									21824x	resistance likely
M28L+Q30R			<2.5x[5]	likely susceptible	<2.5x	likely susceptible
M28S+Q30R										resistance likely
M28T+H58D			>100x[5]	resistance likely	>100x	resistance likely
M28T+L31M	56,000x[16]	resistance likely
M28T+Q30H	76833x[3, 14, 16]	resistance likely	>100x[5]	resistance likely	2835x	resistance likely					2285x	resistance likely
M28T+Q30K	333333x[16]	resistance likely
M28T+Q30R	59333x[14, 16]	resistance likely	>100x[5]	resistance likely	>100x	resistance likely	3576481x	resistance likely	1.6x	likely susceptible
M28T+Y93C			>100x[5]	resistance likely	>100x	resistance likely	639204x	resistance likely	3.1x	resistance possible
M28T+Y93H	59,5000x[16]	resistance likely
M28V+H58R			<2.5x[5]	likely susceptible	<2.5x	likely susceptible
M28V+L31M	583x[16]
M28V+Q30H	383x[16]				<2.5x	likely susceptible			0.5x	likely susceptible
M28V+Q30K	3,333x[16]	resistance likely
M28V+Q30R	350x[16]	resistance likely			<2.5x	likely susceptible	42803x	resistance likely	1.1x	likely susceptible
M28V+R81W			<2.5x[5]	likely susceptible	<2.5x	likely susceptible
M28V+Y93C							11280x	resistance likely
M28V+Y93L							106247x	resistance likely	0.8x	likely susceptible
M28V+Y93N			>100x[5]	resistance likely	>100x	resistance likely
Q30D+Y93N											21,6000x	resistance likely
Q30E+H58D										resistance likely
Q30E+E62V	43833x[16]	resistance likely
Q30E+L31M	82,000x[16]	resistance likely
Q30E+Y93N	296,333x[16]	resistance likely
Q30E+Y93C			>100x[5]	resistance likely	>100x	resistance likely
Q30E+Y93H	67333x[4]	resistance likely
Q30H+H58D	333333x[16]	resistance likely	>100x[5]	resistance likely	>100x	resistance likely
Q30H+L31M	7,500x[16]	resistance likely	>100x[5]	resistance likely	106	resistance likely			2.4x	likely susceptible
Q30H+L31V	75,500[16]	resistance likely									1429x	resistance likely
Q30H+Y93C			>100x[5]	resistance likely
Q30H+Y93F			>100x[5]	resistance likely
Q30H+Y93H	98167x[3]	resistance likely	34960x[3, 5, 9]	resistance likely	2835x	resistance likely			17x	resistance likely
Q30H+Y93N	89,833x[16]	resistance likely			>1000x	resistance likely
Q30K+L31M	172,666x[16]	resistance likely
Q30K+H58D									235x/cRAS	resistance likely
Q30K+Y93H									1786x	resistance likely
Q30L + Y93S	424318x[16]	resistance likely					218x	resistance likely	not viable
Q30L+Y93H	583x[14]	resistance likely	>100x[5]	resistance likely			416x	resistance likely	0.6x	likely susceptible	1235x	resistance likely
Q30N+Y93H										resistance likely
Q30R+E62D	10929x[16]	resistance likely
Q30R+H58D	424318x[14]	resistance likely	>100x[5]	resistance likely	>100x	resistance likely	324315x	resistance likely	108-126x	resistance likely	5882x	resistance likely
Q30R+H58R					<2.5x	likely susceptible
Q30R+I269V							837x	resistance likely
Q30R+L31F			>100x[5]	resistance likely							5571x	resistance likely
Q30R+L31M	195,166x[16]	resistance likely	>100x[5]	resistance likely	198x	resistance likely	510x	resistance likely	3x/cRAS	resistance likely	1196x	resistance likely
Q30R+L31V	333,333x[16, 23]	resistance likely									7143x	resistance likely
Q30R+V75A	850x[16]	resistance likely
Q30R+Y93C	14,166x[15, 16]	resistance likely	1046x[15]	resistance likely	>100x	resistance likely	43833x	resistance likely	3.8x	resistance possible
Q30R+Y93F			>100x[5]	resistance likely					5.5x	resistance possible
Q30R+Y93H	56666x[16]	resistance likely	33691x[1, 3, 9]	resistance likely	>419x	resistance likely	354981x	resistance likely	260x/cRAS	resistance likely
Q30R+Y93L			>100x[5]	resistance likely	>100x	resistance likely
Q30R+Y93N							>40,000x	resistance likely	131x/cRAS	resistance likely
Q30R+Y93S									unfit
Q30Y+F36L									0.8x	likely susceptible
Q30Y+Y93H			>100x[5]	resistance likely	>100x	resistance likely			28x	resistance likely
L31M+E62G			>100x[5]	resistance likely
L31M+H58D	66166x[16]	resistance likely	>100x[5]	resistance likely	>100x	resistance likely			23x/cRAS	resistance likely	2275x	resistance likely
L31M+R81K			>100x[5]	resistance likely
L31M+Y93C	77,333x[16]		>100x[5]	resistance likely	>100x	resistance likely	1995x	resistance likely	6.1x	resistance possible
L31M+Y93H			>44609x[5]	resistance likely					75x	resistance likely	7568x	resistance likely
L31M+Y93N									195x	resistance likely
L31V+V37A	10600x[4]	resistance likely
L31V+H58D			>100x[5]	resistance likely	>100x	resistance likely
L31V+H58P	2400x[16, 23]	resistance likely
L31V+H58R	116x[16]	resistance likely
L31V+Y93C	333,333x[16]	resistance likely	>100x[5]	resistance likely	>100x	resistance likely
L31V+Y93H	>166,666x[16]	resistance likely			>100x/cRAS	resistance likely	32856x	resistance likely	94x	resistance likely	38857x	resistance likely
L31V+Y93N			>44609x[5]	resistance likely	>100x	resistance likely			195x/cRAS	resistance likely	53571x	resistance likely
H54Y+Y93H	5,833x[16]	resistance likely
H58D+Y93C									233x	resistance likely
H58D+Y93H									2238x	resistance likely
H58D+Y93N			>100x[5]	resistance likely	>100x	resistance likely			1969x	resistance likely
H58D+Y93S									1469x	resistance likely
H58P+Y93C			>100x[5]	resistance likely
H58P+Y93H	1200x[4]	resistance likely
E62D+Y93C	1100x[16]	resistance likely
A92T+Y93N									not viable
K24M+Q30R+R81M											69x	resistance likely
K24Q+M28T+L31M											9x	resistance possible
K24T+M28T+Q30R											7000x	resistance likely
P32L+Y93C					>100x	resistance likely			172x	resistance likely
Y93N+I269V							62574x	resistance likely
K24MT+L31IV+Y93H					763x/cRAS	resistance likely
M28A+Q30H+L31V											56000x	resistance likely
M28A+Q30R+L31V										resistance likely
M28G+Q30R+H58C									942x	resistance likely
M28T+Q30H+L31V											56000x	resistance likely
M28T+Q30K+L31M	833,333x[16]	resistance likely
M28T+Q30N+Y93H										resistance likely
M28T+Q30R+H54Y	17,333x[16]	resistance likely
M28T+Q30R+H58D										resistance likely
M28T+Q30R+L31M							435852x	resistance likely	4.6x	resistance possible
M28T+Q30R+L31V											89143x	resistance likely
M28V+Q30H+L31V											2429x	resistance likely
Q30E+L31M+H58P	106,333x[16]	resistance likely
Q30H+E62V+Y93H	70,166x[16]	resistance likely
Q30H+L31M+Y93H										resistance likely
Q30H+L31V+Y93H										resistance likely
Q30H+H58D+Y93H									9357x	resistance likely
Q30K+H58D+E62A									138x/cRAS	resistance likely
Q30R+L31M+H54C	59,833x[16]	resistance likely
Q30R+L31M+H58D									1704x/cRAS	resistance likely	90,000x	resistance likely
Q30R+L31M+Y93C	212,833x[16]	resistance likely					19594x	resistance likely	42x	resistance likely
Q30R+L31M+Y93N	833,333x[16]	resistance likely
Q30R+L31V+H58P	326,500x[16]	resistance likely
Q30R+L31V+Y93C	333,333x[16]	resistance likely
Q30R+Q30D+Y93N
Q30Y+F36L+Y93H									28x	resistance likely
L31M+H58P+Y93C	85,500x[16]	resistance likely
M28V+H58P+E62D+Y93C	66x[16]	resistance possible
M28T+Q30R+L31V+Y93H											714286x	resistance likely